Dendritic cell infiltration and prognosis of early stage breast cancer

Clin Cancer Res. 2004 Nov 15;10(22):7466-74. doi: 10.1158/1078-0432.CCR-04-0684.

Abstract

Purpose: Although dendritic cells (DC) and T cells can infiltrate primary breast carcinoma, it remains unclear whether the immune response influences the clinical outcome.

Experimental design: T lymphocytes and DC infiltration within primary tumors was investigated in 152 patients with invasive nonmetastatic breast cancer. CD1a, CD3, CD68, CD123, CD207/Langerin, and CD208/DC-LAMP expression was assessed with semiquantitative immunohistochemical analysis. Expression of chemokines involved in DC migration (MIP-3a/CCL20, MIP-3b/CCL19, and 6Ckine/CCL21) was also examined. The correlation between these markers and the characteristics of the tumors, as well as relapse-free and overall survival was analyzed. Significant prognostic parameters were then tested in a validation series.

Results: Infiltration by immature CD207/Langerin+ DC was found in a third of the cancers and did not correlate with clinicopathological data. Presence of mature CD208/DC-LAMP+ DC (56%) and CD3+ T cells (82%) strongly correlated with lymph node involvement and tumor grade. Among the chemokines analyzed, only the presence of MIP-3b/CCL19 in 57% of the tumors correlated with prolonged overall survival. CD123+ plasmacytoid DC (pDC) infiltrated 13% of the primary tumors. Their presence was strongly associated with shorter overall survival (93% versus 58% at 60 months) and relapse-free survival (90% versus 37% at 60 months) and was found to be an independent prognostic factor for overall survival and relapse-free survival and confirmed in an independent validation series of 103 patients.

Conclusions: Infiltration by pDC of primary localized breast tumor correlates with an adverse outcome, suggesting their contribution in the progression of breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD
  • Antigens, Surface / biosynthesis
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / pathology*
  • CD3 Complex / biosynthesis
  • Dendritic Cells / cytology*
  • Dendritic Cells / pathology*
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Interleukin-3 Receptor alpha Subunit
  • Lectins, C-Type / biosynthesis
  • Lymphatic Metastasis
  • Mannose-Binding Lectins / biosynthesis
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Receptors, Chemokine / biosynthesis
  • Receptors, Interleukin-3 / biosynthesis
  • Recurrence
  • T-Lymphocytes / cytology
  • Time Factors
  • Treatment Outcome

Substances

  • Antigens, CD
  • Antigens, Surface
  • CD207 protein, human
  • CD3 Complex
  • IL3RA protein, human
  • Interleukin-3 Receptor alpha Subunit
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • Receptors, Chemokine
  • Receptors, Interleukin-3